utorak, 15 Decembar 2015 21:01

Epigenetics and endocrine disrupting chemicals

By Nermina Lamadema, Postdoctoral Research Associate at King's College London


Hormones and Endocrine Disrupting Chemicals (EDC) 

Hormones are natural chemicals produced by endocrine glands and specific organs in the human body influencing its every cell, tissue, organ and function. They act as chemical messengers carrying information through blood stream to the cells and tissues in our body. Everything from our mood to reproduction, metabolism, growth and development is regulated by hormones. There are many different types of hormones and they are designed to affect very specific cells in the body. There are around 20 major hormones secreted into blood stream by the endocrine glands:

  • Pituitary gland secretes growth hormones that stimulate bone and tissue growth; prolactin, hormone involved in milk production in breastfeeding women; anti-diuretic hormone which controls water balance in the body, endorphins involved in pain control; oxytocin responsible for uterus contractions during childbirth, and hormones that act on other endocrine glands in the body such as thyroid (thyrotropin) and adrenal (corticotrophin).
  • Thyroid gland releases thyroxin and triiodothyronine hormones important for cellular metabolism which is a rate at which cell burns fuels from food to produce energy.
  • Parathyroid gland attached to thyroid releases parathyroid hormones to control levels of calcium in the blood.
  • Adrenal gland produces corticosteroid hormones important for a variety of bodily functions ranging from regulation of salt and water balance to stress and immune responses, and sexual development. This is a seat of human ‘Fight or flight’ response regulated by a class of hormones called catecholamine such as epinephrine or adrenaline which in response to stress increase the heart rate and the blood pressure.
  • Pineal gland located in the middle of the brain secretes melatonin a sleep hormone which also helps regulate body clock or circadian rhythms.
  • Reproductive (ovary and testes) glands. In males testes produce androgens – testosterone and ovaries produce oestrogen and progesterone.
  •  Pancreas produces insulin and glucagon to maintain steady levels of glucose in the blood.

Human hormonal system can be disrupted by environmental factors such as exposure to the endocrine disrupting chemicals (EDC). There are well over 800 commercial chemicals in use today which can affect normal functioning of the hormones in the human body by interfering with the hormone receptor binding, storage, transport and biosynthetic pathways. This in turn can lead to disorders during the early development and in adulthood such as genital malformations, pregnancy complications and reproductive system diseases such as breast, ovarian and testicular cancer. How does the diseasedevelop is unknown but it is believed that epigenetics has an important role to play.

Proper hormonal regulation in early stages of development (foetal and babies) is crucial for the tissue and organ growth and development. Early life exposure to the toxic compounds interferes with the endogenous hormones activity which can lead to the severe adverse effects on target organs.

During early development there are two critical stages when the epigenetic marks are established globally and EDC interference at these time points can have detrimental effects leading to the disease across multiple generations.

Three most studied EDCs are bisphenol A (BPA), phthalates and parabens.

Bisphenol A is a polycarbonate industrial chemical first synthesized in 1891 and nowadays used to make plastics. This chemical compound is deeply embedded in the products of the modern consumer society. It is typically found in plastics that make food storage containers, water bottles, food cans lining, some baby bottles and water supply lines amongst many other things. It is used to make other plastics such as epoxy resins, pesticides, fungicides, flame retardant, rubber materials and so on. As the plastics age or through heating i.e. microwave food containers BPA can leech out into the surrounding environment. Studies as early as 1930s have shown that this compound has oestrogen mimicking properties. Numerous animal studies  indicate that  exposure to BPA gives raise to reproductive system diseases mainly breast and prostate cancer, leads to the changes in the brain chemistry, affects immune system development, leads to insulin resistance, birth defects and pregnancy complications. Our environment is contaminated with the BPA to the extent that it can be measured in the rivers ranging in concentrations from 5 to 1900ng/l, in the earth sediments and it does not easily degrade.

Phthalates are chemicals with widespread use ranging from plasticizers to make hard plastics more flexible i.e. use in toys, to use in household cleaners, cosmetics and personal care products. Research on the phthalates toxicology links this chemical exposure to the breast cancer, type II diabetes, asthma, behavioural and neurodevelopment issues, autism ADHD, aberrant reproductive development and male fertility issues.

Parabens are chemicals used as anti-microbialcompounds in cosmetic, pharmaceutical and food industry to prevent growth of yeast and mold. Parabens are added as preservatives to the personal hygiene products such as shampoos, conditioners, lotions, deodorants and antiperspirants.They are oestrogen mimicking compounds capable of binding to the cellular receptors. Parabens have become so much the part of our environment that the urine sample of every adult living in the industrialised countries irrespective of their socio-economic status contains parabens.

How do Endocrine Disruptors work

Endocrine disruptors mimic hormones in the body like oestrogen and androgen or thyroid hormones sometimes leading to their overstimulation.

Alternatively EDCs can bind to the hormone receptors to prevent naturally occurring hormones from binding which can lead to the disruption in intercellular signalling pathways and affect cellular metabolism.  Studies on the effect of EDCs in reproductive systems showthat cell stress responses can be activated affecting hormone metabolism. Diagram below shows how a chemical can mimic and prevent binding of natural hormones to their receptors.

 

Epigenetic Inheritance

Early development involves three key epigenetic events which can be affected by EDCs and they are: DNA methylation responsible for silencing of an extra X chromosome in females in early development. DNA methylation and demethylation is regulated by enzymes which can also be subjected to alterations upon EDC exposure. Histone modification is a second epigenetic mechanism which can be compromised upon EDC exposure. Finally long non coding RNA responsible for transgenerational epigenetic inheritance can also be affected.

In the developed countries last few decades have seen a marked decrease in the male fertility with around 50% decrease in sperm concentration and lower sperm quality. Male infertility is associated with the abnormal methylation patterns. In males during early foetal development EDCs can affect methylation globally resulting in infertility. Many adult life diseases such as neurodegenerative, pulmonary and cardiovascular disorders and cancers i.e. breast cancer have altered epigenome upon EDC exposure. For example when breast epithelial cells are exposed to BPA, changes can be observed in the genes coding for enzymes that are key epigenetic regulators.

From the conception to advanced age the effect of environmental exposure on human health is complex and varied. Potentially reversible nature of epigenetics means that there might be a scope for the prevention and early treatment of environmentally induced diseases. However, it may be quite challenging measuring these changes during the individual’s life span. Lifestyle factors such as diet, physical activity, and circadianrhythms can modify the effects of the exposure and influence epigenome.

The EDC exposure costs EU in excess of €157bn according to the US based endocrine society. These costs are related to healthcare expenses, loss of earning potential and productivity. Recently an EU report based on scientific research into the EDCs as well as pesticide and biocides was blocked according to NGOs by top EU officials under the pressure from chemical industry and agricultural lobby. The paper suggested ways of categorizing EDCs which would have seen EU banning some of the hazardous substances but due to the pressure it was suppressed allowing their continued use. EU on the other hand states that their decision was based on sound coherent science which is sometimes highly complex. In the meantime whilst the sometimes heavily bureaucratic EU machine weighs up pros and cons of continued use of these chemicals it is up to individuals with a consumer power to start reclaiming their future. As the mothers and responsible members of the human society we should ask ourselves is this the world we want  to leave in inheritance for our children or are we ready to educate ourselves and armed with scientific facts become more consumer savvy and reclaim this world for our children sake. 

Ovaj članak na bosanskom jeziku možete pročitati u porodičnom magazinu za afirmaciju kulture življenja AŠK, broj 11, decembar 2015.

 

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